1. Field of the Invention
The present invention relates to a method of preventing or treating a microbial infection, in particular, an infection by Pneumocystis carinii or Toxoplasma gondii.
2. Background Information
Pneumocystis carinii and Toxoplasma gondii are pathogens of immunosuppressed hosts which have become more important clinically with the Acquired Immunodeficiency Syndrome (AIDS) epidemic. These pathogens cause serious infections in immunosuppressed patients including patients with cancer, organ transplants and AIDS. Currently, available agents for treatment and prevention of these infections in immunosuppressed patients are poorly tolerated by many patients, especially those with AIDS. Furthermore, administration of available agents is often via difficult routes such as intravenously or by aerosol.
Studies in rodents and humans have resulted in the implication that P. carinii possess a pathway for de novo folate synthesis that is susceptible to sulfonamides, and the enzyme dihydrofolate reductase (DHFR), which is susceptible to trimethoprim. More recent studies have documented the presence of these pathways in P. carinii and T. gondii. Since mammalian cells can not synthesize folates de novo, these metabolic pathways are an ideal target for the development of more effective anti-pneumocystis and anti-toxoplasma agents since the host would not be affected by the targeted action of such therapeutic agents.
The present inventors have discovered an agent having antimicrobial activity, (particularly anti-pneumocystis activity), suitable for use in patients, especially immunosuppressed patients.